Oxygen-independent organic photosensitizer with ultralow-power NIR photoexcitation for tumor-specific photodynamic therapy

Yufu Tang, Yuanyuan Li, Bowen Li, Wentao Song, Guobin Qi, Jianwu Tian, Wei Huang, Quli Fan () and Bin Liu ()
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Yufu Tang: National University of Singapore
Yuanyuan Li: Nanjing University of Posts and Telecommunications
Bowen Li: National University of Singapore
Wentao Song: National University of Singapore
Guobin Qi: National University of Singapore
Jianwu Tian: National University of Singapore
Wei Huang: Nanjing University of Posts and Telecommunications
Quli Fan: Nanjing University of Posts and Telecommunications
Bin Liu: National University of Singapore

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O2− and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H2O into •O2− and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O2− and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H2O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O2− and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm−2. The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT.

Date: 2024
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DOI: 10.1038/s41467-024-46768-w

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